The objective of this proposal is to determine the role of prostaglandins in the maintenance of normal pulmonary vasomotor tone and in the development of pulmonary vasoconstriction during alveolar hypoxia. We also will determine whether vasodilator agents which reduce pulmonary tone during hypoxic pulmonary vasoconstriction exert their effect through the prostaglandin system. Two animal models of enhanced pulmonary tone during hypoxia will be used: The intact, closed-chested dog ventilated with 10% oxygen for three hours, and the isolated, perfused rabbit lung ventilated with 10% oxygen. In all experiments we will measure ventilatory and circulatory parameters and either circulating of effluent levels of prostaglandin metabolites, respectively, before and during hypoxia and after the administration of various vasodilator agents. Prostaglandins or their metabolites will be measured using radioimmunoassay techniques. These studies will provide a clearer understanding of the mechanisms responsible for pulmonary vascular responsiveness, and may provide a rationale for an approach to the prevention and management of pulmonary hypertension complicating acute and chronic hypoxic lung diseases.